Imidazole → ((2-Bromo-6-nitrobenzyl)oxy)(tert-butyl)dimethylsilane

A 150-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet was charged with a solution of 114b (11.6 g, 42.3 mmol) in a mixture of THF (20 mL), ethanol (20 mL) and water (20 mL). Lithium hydroxide monohydrate (7.00 g, 167.0 mmol) was added and the reaction was stirred at room temperature for 1 h. After this time, the reaction mixture was partitioned between water (200 mL) and ethyl acetate (400 mL). The layers were separated, and the aqueous phase was extracted with ethyl acetate (2×200 mL). The organic extracts were combined, dried over sodium sulfate, filtered and concentrated under reduced pressure. The resulting residue was dissolved in anhydrous methylene chloride (50 mL). Imidazole (14.4 g, 68.0 mmol) was added, followed by dropwise addition of tert-butyldimethylchlorosilane (16.0 g, 106 mmol). The mixture was stirred at room temperature for 14 h. After this time, water (200 mL) was added and the layers separated. The aqueous layer was extracted with methylene chloride (2×200 mL) and the combined organic layers were washed with brine, and dried over sodium sulfate. The drying agent was removed by filtration and the filtrate was concentrated under reduced pressure. The resulting residue was purified by flash chromatography to afford an 89% yield (13.1 g) of 114c as a white semi-solid: 1H NMR (500 MHz, CDCl3) δ 7.67 (d, 1H, J=8.5 Hz), 7.54 (d, 1H, J=8.5 Hz), 7.18 (t, 1H, J=8.0 Hz), 4.96 (s, 2H), 0.80 (s, 9H), 0.007 (s, 6H).

1. customA 150-mL single-neck round-bottomed flask equipped with a magnetic stirrer and nitrogen inlet
2. customAfter this time, the reaction mixture was partitioned between water (200 mL) and ethyl acetate (400 mL)
3. customThe layers were separated
4. extractionthe aqueous phase was extracted with ethyl acetate (2×200 mL)
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. dissolutionThe resulting residue was dissolved in anhydrous methylene chloride (50 mL)
9. stirringThe mixture was stirred at room temperature for 14 h
10. customthe layers separated
11. extractionThe aqueous layer was extracted with methylene chloride (2×200 mL)
12. washthe combined organic layers were washed with brine
13. dry with materialdried over sodium sulfate
14. customThe drying agent was removed by filtration
15. concentrationthe filtrate was concentrated under reduced pressure
16. customThe resulting residue was purified by flash chromatography

ORD record

ord-9b71c80e933e482fbcc9ae2fce50b14e

Source dataset

uspto-grants-2016_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09249123B2